NCT00994071

A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors

Completed Phase 1 Last updated 9 December 2019

What this trial tests

Phase 1 trial testing Temozolomide in Medulloblastoma in 9 participants. Completed in 19 March 2013.

Timeline

22 September 2009

19 March 2013

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	9
Start date	22 September 2009
Estimated completion	19 March 2013
Sites	1 location across United States

Drugs / interventions tested

• Temozolomide (temozolomide) — full drug profile →
• ABT-888 — full drug profile →

Conditions studied

• Medulloblastoma — all drugs for Medulloblastoma →
• Pontine Glioma — all drugs for Pontine Glioma →
• Ependymoma — all drugs for Ependymoma →
• Astrocytoma — all drugs for Astrocytoma →

Sponsor

National Cancer Institute (NCI)

Who can join

Under 21, any sex, with Medulloblastoma or Pontine Glioma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

\- An experimental drug called ABT-888 has been studied in combination with temozolomide (a type of chemotherapy) in adults who have certain kinds of cancer. ABT-88 has been shown to increase tumor sensitivity to temozolomide and improve treatment outcomes in people who have cancer. More research is needed to determine if this combination of drugs will work well as an effective treatment for children who have brain tumors. This will be the first time this combination has been studied in pediatric patients.

Objectives:

* To determine the maximum doses of ABT-888 and temozolomide when given in combination in children with brain tumors.
* To learn how children metabolize and clear ABT-888 from their bodies so that appropriate doses of this medication can be recommended for future clinical trials of this drug.
* To learn what side effects may occur when ABT-888 and temozolomide are given together.
* To learn how certain tumors respond to this combination of drugs by studying the characteristics of these tumors in a laboratory.

Eligibility:

\- Individuals less than 21 years of age who have been diagnosed with a cancer of the nervous system (including brain and brain stem tumors) that has not responded to standard therapy.

Design:

* Before beginning the study, participants will have a full medical history and physical examination, and may also be required to have scans of the brain and spine or provide samples of cerebrospinal fluid.
* Treatment will consist of up to 13 28-day cycles of therapy, for a total of 52 weeks (1 year). Participants will receive a dose of ABT-888 twice daily for 5 days, and will receive a dose of temozolomide once daily for 5 days, every 28 days. The morning dose of ABT-888 will be given 60-90 minutes before the dose of temozolomide.
* Participants will have routine blood tests at least once a week throughout the treatment cycles, and will have scans of the brain and spine performed as required by the researchers.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting DNA damage response in cancer therapy.
   Hosoya N, Miyagawa K. · · 2014 · cited 232× · PMID 24484288 · DOI 10.1111/cas.12366
2. Advances and perspectives of PARP inhibitors.
   Yi M, Dong B, Qin S, Chu Q, et al · · 2019 · cited 83× · PMID 31737426 · DOI 10.1186/s40164-019-0154-9
3. PARP Inhibitors in Glioma: A Review of Therapeutic Opportunities.
   Sim HW, Galanis E, Khasraw M. · · 2022 · cited 36× · PMID 35205750 · DOI 10.3390/cancers14041003
4. Targeting the DNA Damage Response for the Treatment of High Risk Neuroblastoma.
   Southgate HED, Chen L, Curtin NJ, Tweddle DA. · · 2020 · cited 28× · PMID 32309213 · DOI 10.3389/fonc.2020.00371
5. Research progress of anti-glioma chemotherapeutic drugs (Review).
   Zhou YS, Wang W, Chen N, Wang LC, et al · · 2022 · cited 23× · PMID 35362540 · DOI 10.3892/or.2022.8312
6. Pharmacodynamic endpoints as clinical trial objectives to answer important questions in oncology drug development.
   Parchment RE, Doroshow JH. · · 2016 · cited 22× · PMID 27663483 · DOI 10.1053/j.seminoncol.2016.07.002
7. Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases.
   Mekhaeil M, Dev KK, Conroy MJ. · · 2022 · cited 20× · PMID 35158955 · DOI 10.3390/cancers14030687
8. BRCAness as a Biomarker of Susceptibility to PARP Inhibitors in Glioblastoma Multiforme.
   Xavier MA, Rezende F, Titze-de-Almeida R, Cornelissen B. · · 2021 · cited 16× · PMID 34439854 · DOI 10.3390/biom11081188